This is a proposal to establish a Center of Biomedical Research Excellence (COBRE) focusing on Cancer Biology with emphasis on the identification, functional characterization, and targeting of tumor specific markers and antigens. Our center will use cell and molecular biology, immunology, nanoparticle technology, and animal models to examine the development, detection, and treatment of human cancer. Five research projects are included. The goals of Project 1 (Meena Jaggi, PhD) are to understand the effects of protein kinase Dl on (3- catenin-mediated signaling and to determine if PKD1 expression influences tumor progression through this pathway. For Project 2 (Kristi Egland, PhD) a large number of membrane and secreted proteins that are expressed at elevated levels in prostate cancer cells were identified. This information will be used to develop a new diagnostic test for prostate cancer that detects autoantibodies in patient serum. Project 3 (Satoshi Nagata, PhD) will develop a panel of monoclonal antibodies to surface antigens that are highly expressed in B cell malignancies. These antibodies will be tested for their potential use in immunotherapies. Project 4 (Subhash Chauhan, PhD) will develop novel methods of treatment and drug delivery for pancreatic cancer. The goal will be to combine radioimmunotherapy and nanoparticle technology for highly specific delivery of cytotoxic compounds. Project 5 (William Spanos, MD) will focus on the role of the immune response in tumor clearance following treatment of head and neck squamous cell carcinoma. A strong mentoring plan will take advantage of the experience of an outstanding group of senior faculty with active research programs. Mentors will provide guidance for research design, manuscript preparation, grant applications, and other crucial aspects of career development. An EAC consisting of five internationally recognized scientists with broad experience in basic, translational, and clinical research has been assembled. Research capabilities will be supported by core facilities in Molecular Pathology, Flow Cytometry, Tumor Biology, and Imaging. We will recruit 3 high quality junior investigators and 1 established investigator. We will train students and post-doctoral fellows, support a seminar series, and fund pilot research projects in the field of cancer research.